Psoriasis is a chronic skin disease, and remains a disfiguring and disabling cutaneous impairment to millions of persons. The cause of psoriasis is unknown, and therefore prevention is impossible. Therapy has necessarily been empiric. One method of treatment employs the systemic use of antimitotic drugs such as methotrexate to induce remissions of the lesions. However, the use of methotrexate is accompanied by acute and chronic toxicity to tissues other than skin, and therefore, has been discredited. It is imperative then that other means of therapy by external delivery of drugs be found which either confine toxicity chiefly to the skin, or are non-toxic.
We have disclosed, in prior patents, several methods for treating psoriasis. For example, in our prior patent application entitled TREATMENT OF PSORIASIS, Ser. No. 371,516, filed June 19, 1973, now U.S. Pat. No. 3,904,766, we described the use of mechlorethamine hydrochloride ointment to treat psoriasis by topical application. In our prior patent application entitled TREATMENT OF PSORIASIS WITH N-METHYLDIETHANOLAMINE, Ser. No. 455,665, filed Mar. 28, 1974, now U.S. Pat. No. 3,920,840, we described our discovery that psoriatic conditions could also be successfully treated by utilizing one of the degradation products of mechlorethamine hydrochloride, N-methyldiethanolamine, a compound which is primarily antiinflammatory. In our prior patent application entitled TREATMENT OF PSORIASIS WITH 6-AMINONICOTINAMIDE AND THIONICOTINAMIDE, Ser. No. 601,411, filed Aug. 4, 1975, now U.S. Pat. No. 4,067,975, we described the use of 6-aminonicotinamide and thionicotinamide in the treatment of psoriasis by topical application. In our prior patent application entitled TREATMENT OF PSORIASIS WITH 6-SUBSTITUTED NICOTINAMIDES, 2-SUBSTITUTED PYRAZINAMIDES AND CLOSELY RELATED COMPOUNDS, Ser. No. 715,131, filed Aug. 17, 1976, now U.S. Pat. No. 4,141,977, we described the use of 6-aminonicotinamide derivatives and related compounds in the topical treatment of psoriasis.
Corticosteriods are well known antiinflammatory drugs which have been used for topical and systemic treatment of psoriasis. The results of using corticosteroids in topical treatment of psoriasis, however, have been variable and unpredictable. In some cases topical corticosteroids seemed to improve and eradicate the psoriatic lesions, but in other cases corticosteroids appear to be ineffective on topical administration. Drug resistance and rebound worsening are also common features when corticosteriods alone are used in the treatment of psoriasis.
Because psoriatic lesions consist of both erythema (red, inflamed) and thick scales we conceive the likelihood that anti-scaling drugs in corticosteroid preparations might facilitate the remission of psoriatic lesions.
In our prior patent application entitled TREATMENT OF ICHTHYOSIFORM DERMATOSES, Ser. No. 394,269, filed Sept. 4, 1973, now U.S. Pat. No. 3,879,537, we described and claimed the use of certain .alpha.-hydroxy acids, .alpha.-keto acids and related compounds for topical treatment of fish-scale like ichthyotic conditions in humans. In our patent application entitled TREATMENT OF DISTURBED KERATINIZATION, Ser. No. 445,231, filed Feb. 25, 1974, now U.S. Pat. No. 3,920,835, we described and claimed the use of these certain .alpha.-hydroxy acids .alpha.-keto acids and their derivatives for topical treatment of dandruff, acne, and palmar and plantar hyperkeratosis.
In our copending application Ser. No. 870,114, filed Jan. 17, 1978, the disclosure of which is hereby incorporated by reference, there is described the discovery that certain .alpha.-hydroxy acids and related compounds and reaction products of these compounds and certain organic amines or ammonium hydroxide are effective in the topical treatment of dry skin conditions.
Specifically, the acids and related compounds described were citric acid; glycolic acid; glucuronic acid; galacturonic acid; lactones, such as, glucuronolactone, and gluconolactone; .alpha.-hydroxybutyric acid; .alpha.-hydroxy-isobutyric acid; lactic acid; malic acid; mandelic acid; mucic acid; pyruvic acid; esters thereof, such as, methyl pyruvate and ethyl pyruvate; compounds related thereto, such as .beta.-phenyllactic acid and .beta.-phenylpyruvic acid; .beta.-hydroxybutyric acid; saccharic acid, tartaric acid; and tartronic acid.
Basic reactants described therein included ammonium hydroxide, organic primary, secondary or tertiary amines, such as, alkylamines, alkanolamines, diamines, dialkyl amines, dialkanolamines, alkylalkanolamines, trialkylamines, trialkanolamines, dialkylalkanolamines, and alkyl dialkanolamines wherein the alkyl or alkanol substituent has from 1 to 8 carbon atoms.
In our copending patent application Ser. No. 948,489, filed Oct. 4, 1978, the disclosure of which is hereby incorporated by reference, we describe our discovery that certain free acids, related compounds and reaction products with certain organic or inorganic bases were effective upon topical application to alleviate the symptoms of actinic and nonactinic keratoses.
Specifically, the free acids and related compounds described were citric acid; glycolic acid; glucuronic acid; gluconic acid; galacturonic acid; glucoheptonic acid; lactones, such as, glucoheptono 1,4 lactone, gluconolactone, glucuronolactone; .alpha.-hydroxybutyric acid; .alpha.-hydroxyisobutyric acid; .alpha.-hydroxyisocaproic acid; .alpha.-hydroxyisovaleric acid; lactic acid; atrolactic acid; malic acid; mandelic acid; mucic acid; pyruvic acid; esters thereof, such as, methyl pyruvate, ethyl pyruvate, and isopropyl pyruvate; saccharic acid; its lactone, saccharic acid, 1,4-lactone; tartaric acid, tartronic acid; and related compounds, such as, .beta.-hydroxybutyric acid; .beta.-phenyl-lactic acid, .beta.-phenylpyruvic acid.
The list of acids and related materials disclosed in our application Ser. No. 948,489, included the compounds identified application Ser. No. 870,114, and in addition gluconic acid, glucoheptonic acid, glucoheptono 1,4-lactone, .alpha.-hydroxy-isocaproic acid, .alpha.-hydroxyisovaleric acid, atrolactic acid, isopropyl pyruvate, and saccharic 1,4-lactone. This list then totals twenty-nine related compounds found to be effective against skin keratoses.
We also described in our patent application TREATMENT OF BODY ODOR AND DISTURBED KERATINIZATION, Ser. No. 703,188, filed July 7, 1976, now U.S. Pat. No. 4,053,630, the discovery that Cysteic acid, Cysteinesulfinic acid, and Homocysteic acid and metal chelates thereof are effective on topical application against certain skin conditions including acne, dandruff and ichthyosis. We further described in our copending application Ser. No. 949,536, filed Oct. 10, 1978, the disclosure of which is hereby incorporated by reference, that the above acids or reaction products with certain inorganic or organic bases were additionally effective against dry skin, actinic and nonactinic keratoses, warts, and palmar and plantar keratosis.